AB1499 TWO DISTINCT SUBSETS OF IMMUNE CHECKPOINT INHIBITOR-INDUCED INFLAMMATORY ARTHRITIS DEFINED BY LATENT CLASS ANALYSIS
Authors: L. Cappelli, J. Perin, C. Bingham, A. Shah
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Immune checkpoint inhibitors (ICI) can lead to immune related adverse events, including inflammatory arthritis (IA). ICI-IA is heterogeneous and can be severe, even persisting after ICI cessation. Understanding the clinical heterogeneity of ICI-IA can guide future studies of pathogenesis and identify relevant groups for clinical trials. <h3>Objectives</h3> To define clinically relevant subgroups within ICI-IA using a data driven approach and to examine differences between subgroups. <h3>Methods</h3> Participants were &gt;=18 years old, treated with anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 agents alone or in combination, and had ICI-IA diagnosed by a rheumatologist. We used information from the baseline rheumatology visit (patient reported symptoms, physical exam features, physician global arthritis rating, and laboratory studies) to cluster patients with latent class analysis. The Bayesian Information Criteria (BIC) was used to select the number of phenotypes with the lowest BIC. We then compared demographics, cancer type and treatments, and IA treatments and outcomes between the estimated phenotypes. Next, we estimated the association between these features of interest and the likelihood of being in the group with the most severe IA symptoms using logistic regression. <h3>Results</h3> Of the 126 patients with ICI-IA, the majority of participants were female (56%) and white (92%). Most patients had a moderate or high level of disease activity by CDAI; the mean CDAI was 16.98 (SD 10.2). Eighteen variables were used to estimate latent classes. Two distinct phenotypes were indicated by the BIC; 61 patients are estimated to be the first phenotype and 65 the second phenotype. Participants in the second phenotype were more likely to have high baseline levels of patient reported pain, stiffness, and disease activity (Figure 1). There were no significant differences in age, gender, race, ethnicity or marital status between the two phenotype groups. Patients in phenotype 2 were more likely to require steroids as compared to patients in phenotype 1 and were more likely to have persistent IA (table 1). Type of ICI therapy, type of cancer, prior chemotherapy or radiation did not differ between the groups. When adjusted for age, gender, baseline steroid use, these variables remained significantly associated with the second phenotype. <h3>Conclusion</h3> Two separate phenotypes of ICI-IA were determined with latent class analysis. Those in the group with more severe features at baseline were more likely to need corticosteroids and to have persistent IA, but there was no association with cancer history or treatment. Future research can interrogate underlying genetic and immunologic differences between groups. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Laura Cappelli Grant/research support from: Bristol-Myers Squibb, Jamie Perin: None declared, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Ami Shah Grant/research support from: Kadmon Corporation, Eicos Sciences, Medpace LLC, Arena Pharmaceuticals.